Ahlqvist Kati J, Suomalainen Anu, Hämäläinen Riikka H
Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland; Helsinki University Central Hospital, Department of Neurology, Helsinki, Finland; Neuroscience Center, University of Helsinki, Helsinki, Finland.
Biochim Biophys Acta. 2015 Nov;1847(11):1380-6. doi: 10.1016/j.bbabio.2015.05.014. Epub 2015 May 23.
Decline in metabolism and regenerative potential of tissues are common characteristics of aging. Regeneration is maintained by somatic stem cells (SSCs), which require tightly controlled energy metabolism and genomic integrity for their homeostasis. Recent data indicate that mitochondrial dysfunction may compromise this homeostasis, and thereby contribute to tissue degeneration and aging. Progeroid Mutator mouse, accumulating random mtDNA point mutations in their SSCs, showed disturbed SSC homeostasis, emphasizing the importance of mtDNA integrity for stem cells. The mechanism involved changes in cellular redox-environment, including subtle increase in reactive oxygen species (H₂O₂and superoxide anion), which did not cause oxidative damage, but disrupted SSC function. Mitochondrial metabolism appears therefore to be an important regulator of SSC fate determination, and defects in it in SSCs may underlie premature aging. Here we review the current knowledge of mitochondrial contribution to SSC dysfunction and aging. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.
新陈代谢的衰退和组织再生潜能的下降是衰老的常见特征。组织再生由体细胞干细胞（SSC）维持，这些体细胞干细胞需要严格控制能量代谢和基因组完整性以维持其稳态。最近的数据表明，线粒体功能障碍可能会破坏这种稳态，从而导致组织退化和衰老。早衰突变小鼠在其体细胞干细胞中积累随机的线粒体DNA点突变，表现出体细胞干细胞稳态紊乱，强调了线粒体DNA完整性对干细胞的重要性。其机制涉及细胞氧化还原环境的变化，包括活性氧（过氧化氢和超氧阴离子）的细微增加，这并未导致氧化损伤，但破坏了体细胞干细胞的功能。因此，线粒体代谢似乎是体细胞干细胞命运决定的重要调节因子，体细胞干细胞中线粒体代谢的缺陷可能是早衰的基础。在此，我们综述了线粒体对体细胞干细胞功能障碍和衰老影响的当前知识。本文是名为《衰老中的线粒体功能障碍》特刊的一部分。
